Michael J McKenna

Harvard University, Cambridge, Massachusetts, United States

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Publications (129)240.32 Total impact

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    ABSTRACT: Hypothesis: Drug delivered to the oval window can diffuse to the apex of the human cochlea. Background: We have previously demonstrated that zoledronate, a nitrogen-containing bisphosphonate, can arrest the sensorineural hearing loss in cochlear otosclerosis. We have also shown that, in animals, delivery of bisphosphonate into the cochlea can dramatically increase delivery efficiency. Intracochlear drug delivery has the potential to increase local concentration of drug while decreasing the risk of systemic toxicity. In the present study, a fluorescently labeled bisphosphonate compound (6-FAM-ZOL) was introduced into the human cochlea through the oval window and its distribution within the temporal bone was quantified. Methods: In three fresh human temporal bones, we introduced 6-FAM-ZOL via the oval window. We compared these specimens to control specimens treated with artificial perilymph alone. Specimens were then processed, embedded into methyl methacrylate, and ground to the mid-modiolar axis. We quantified the fluorescence in confocal images. Results: We found 6-FAM-ZOL to be distributed up to the apical cochlear turn. In specimens treated with 6-FAM-ZOL, we identified a strong baso-apical gradient of fluorescent signal along the lateral cochlear wall and the modiolus both in the scala vestibuli and in the scala tympani. Conclusion: Bisphosphonate introduced via the oval window in the human cochlea can be delivered up to the apical cochlear turn. Interscalar communication is likely to play an important role in determining patterns of drug delivery in the inner ear.
    No preview · Article · Mar 2016 · Otology & Neurotology
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    ABSTRACT: The anatomical and pharmacological inaccessibility of the inner ear is a major challenge in drug-based treatment of auditory disorders. This also makes pharmacokinetic characterization of new drugs with systemic delivery challenging, because efficacy is coupled with how efficiently a drug can reach its target. Direct delivery of drugs to cochlear fluids bypasses pharmacokinetic barriers and helps to minimize systemic toxicity, but anatomical barriers make administration of multiple doses difficult without an automated delivery system. Such a system may be required for hair-cell regeneration treatments, which will likely require timed delivery of several drugs. To address these challenges, we have developed a micropump for controlled, automated inner-ear drug delivery with the ultimate goal of producing a long-term implantable/wearable delivery system. The current pump is designed to be used with a head mount for guinea pigs in preclinical drug characterization experiments. In this system, we have addressed several microfluidic challenges, including maintaining controlled delivery at safe, low flow rates and delivering drug without increasing the volume of fluid in the cochlea. By integrating a drug reservoir and all fluidic components into the microfluidic structure of the pump, we have made the drug delivery system robust compared to previous systems that utilized separate, tubing-connected components. In this study, we characterized the pump's unique infuse-withdraw and on-demand dosing capabilities on the bench and in guinea pig animal models. For the animal experiments, we used DNQX, a glutamate receptor antagonist, as a physiological indicator of drug delivery. DNQX suppresses compound action potentials (CAPs), so we were able to infer the distribution and spreading of the DNQX over time by measuring the changes in CAPs in response to stimuli at several characteristic frequencies. .
    No preview · Article · Dec 2015 · Lab on a Chip
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    ABSTRACT: Objectives: Ossicular discontinuity may be complete, with no contact between the disconnected ends, or partial, where normal contact at an ossicular joint or along a continuous bony segment of an ossicle is replaced by soft tissue or simply by contact of opposing bones. Complete ossicular discontinuity typically results in an audiometric pattern of a large, flat conductive hearing loss. In contrast, in cases where otomicroscopy reveals a normal external ear canal and tympanic membrane, high-frequency conductive hearing loss has been proposed as an indicator of partial ossicular discontinuity. Nevertheless, the diagnostic utility of high-frequency conductive hearing loss has been limited due to gaps in previous research on the subject, and clinicians often assume that an audiogram showing high-frequency conductive hearing loss is flawed. This study aims to improve the diagnostic utility of high-frequency conductive hearing loss in cases of partial ossicular discontinuity by (1) making use of a control population against which to compare the audiometry of partial ossicular discontinuity patients and (2) examining the correlation between high-frequency conductive hearing loss and partial ossicular discontinuity under controlled experimental conditions on fresh cadaveric temporal bones. Furthermore, ear-canal measurements of umbo velocity and wideband acoustic immittance measurements were investigated to determine the usefulness regarding diagnosis of ossicular discontinuity. Design: The authors analyzed audiograms from 66 patients with either form of surgically confirmed ossicular discontinuity and no confounding pathologies. The authors also analyzed umbo velocity (n = 29) and power reflectance (n = 12) measurements from a subset of these patients. Finally, the authors performed experiments on six fresh temporal bone specimens to study the differing mechanical effects of complete and partial discontinuity. The mechanical effects of these lesions were assessed via laser Doppler measurements of stapes velocity. In a subset of the specimen (n = 4), wideband acoustic immittance measurements were also collected. Results: (1) Calculations comparing the air-bone gap (ABG) at high and low frequencies show that when high-frequency ABGs are larger than low-frequency ABGs, the surgeon usually reported soft-tissue bands at the point of discontinuity. However, in cases with larger low-frequency ABGs and flat ABGs across frequencies, some partial discontinuities as well as complete discontinuities were reported. (2) Analysis of umbo velocity and power reflectance (calculated from wideband acoustic immittance) in patients reveal no significant difference across frequencies between the two types of ossicular discontinuities. (3) Temporal bone experiments reveal that partial discontinuity results in a greater loss in stapes velocity at high frequencies when compared with low frequencies, whereas with complete discontinuity, large losses in stapes velocity occur at all frequencies. Conclusion: The clinical and experimental findings suggest that when encountering larger ABGs at high frequencies when compared with low frequencies, partial ossicular discontinuity should be considered in the differential diagnosis.
    No preview · Article · Oct 2015 · Ear and hearing
  • Jennifer T. O’Malley · Joseph B. Nadol · Michael J. McKenna

    No preview · Article · Oct 2015 · Otology & Neurotology
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    ABSTRACT: OBJECTIVE:: Health utility value (HUV) is an outcome measure used to calculate quality adjusted life years (QALYs) and to determine cost-effectiveness of medical treatments. Herein, we measure HUV in patients with superior canal dehiscence syndrome (SCDS) before and after surgical repair. Health utility values of patients with SCDS are compared to normative data of the general United States population. STUDY DESIGN:: Retrospective review of prospectively collected data. PATIENTS:: Adult patients with SCDS. SETTING:: Tertiary referral center. INTERVENTIONS:: SCD repair via middle fossa craniotomy or transmastoid approaches. MAIN OUTCOME MEASURE:: Primary outcome: change in HUV, as measured by the Short-Form 6-Dimension questionnaire. Secondary outcomes: autophony index (AI), dizziness handicap inventory (DHI), and hearing handicap inventory (HHI). RESULTS:: Fifty-one patients with SCDS were enrolled, 23 underwent surgical repair. Mean HUV in patients with SCDS is significantly lower than the general U.S. population: 0.68 (SD?=?0.13) versus 0.80 (0.29), p? ?0.14. Nonoperated patients had no significant change in HUV during a mean follow-up period of 21 months (range 9–39), p?=?0.33. CONCLUSIONS:: SCDS patients have significantly lower HUV compared with the general U.S. population. HUV demonstrated improvement after surgery. Nonoperated patients have ongoing impaired quality of life.
    No preview · Article · Oct 2015 · Otology & Neurotology
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    ABSTRACT: Local delivery of bisphosphonates results in superior localization of these compounds for the treatment of cochlear otosclerosis, without ototoxicity. Otosclerosis is a common disorder of abnormal bone remodeling within the human otic capsule. It is a frequent cause of conductive hearing loss from stapes fixation. Large lesions that penetrate the cochlear endosteum and injure the spiral ligament result in sensorineural hearing loss. Nitrogen-containing bisphosphonates (e.g., zoledronate) are potent inhibitors of bone remodeling with proven efficacy in the treatment of metabolic bone diseases, including otosclerosis. Local delivery to the cochlea may allow for improved drug targeting, higher local concentrations, and the avoidance of systemic complications. In this study, we use a fluorescently labeled bisphosphonate compound (6-FAM-ZOL) to determine drug localization and concentration within the otic capsule. Various methods for delivery are compared. Ototoxicity is evaluated by auditory brainstem responses and distortion product otoacoustic emissions. 6-FAM-ZOL was administered to guinea pigs via intraperitoneal injection, placement of alginate beads onto the round window membrane, or microfluidic pump infusion via a cochleostomy. Hearing was evaluated. Specimens were embedded into resin blocks, ground to a mid-modiolar section, and quantitatively imaged using fluorescence microscopy. There was a dose-dependent increase in fluorescent signal after systemic 6-FAM-ZOL treatment. Local delivery via the round window membrane or a cochleostomy increased delivery efficiency. No significant ototoxicity was observed after either systemic or local 6-FAM-ZOL delivery. These findings establish important preclinical parameters for the treatment of cochlear otosclerosis in humans.
    No preview · Article · May 2015 · Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
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    ABSTRACT: One of the major challenges in treatment of auditory disorders is that many therapeutic compounds are toxic when delivered systemically. Local intracochlear delivery methods are becoming critical in emerging treatments and in drug discovery. Direct infusion via cochleostomy, in particular, is attractive from a pharmacokinetics standpoint, as there is potential for the kinetics of delivery to be well-controlled. Direct infusion is compatible with a large number of drug types, including large, complex molecules such as proteins and unstable molecules such as siRNA. In addition, hair-cell regeneration therapy will likely require long-term delivery of a timed series of agents. This presents unknown risks associated with increasing the volume of fluid within the cochlea and mechanical damage caused during delivery. There are three key requirements for an intracochlear drug delivery system: (1) a high degree of miniaturization (2) a method for pumping precise and small volumes of fluid into the cochlea in a highly controlled manner, and (3) a method for removing excess fluid from the limited cochlear fluid space. To that end, our group is developing a head-mounted microfluidics-based system for long-term intracochlear drug delivery. We utilize guinea pig animal models for development and demonstration of the device. Central to the system is an infuse-withdraw micropump component that, unlike previous micropump-based systems, has fully integrated drug and fluid storage compartments. Here we characterize the infuse-withdraw capabilities of our micropump, and show experimental results that demonstrate direct drug infusion via cochleostomy in animal models. We utilized DNQX, a glutamate receptor antagonist that suppresses CAPs, as a test drug. We monitored the frequency-dependent changes in auditory nerve CAPs during drug infusion, and observed CAP suppression consistent with the expected drug transport path based on the geometry and tonotopic organization of the cochlea.
    No preview · Article · Apr 2015 · Biomedical Microdevices
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    ABSTRACT: Objective: Studies have reported high early success rates in rectifying dizziness and autophony after primary repair of superior canal dehiscence (SCD). We sought to identify the prevalence of dizziness and autophony at later time points in patients who had undergone SCD repair. We also assessed any problems with hearing in this population, along with prevalence of headaches and decreases in overall quality of life. Study Quality Design: Identification of patients via retrospective chart review, followed by administration of multiple validated surveys.
    No preview · Article · Aug 2014 · Otology & Neurotology
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    ABSTRACT: Objective: Surgical access to repair a superior canal dehiscence (SCD) is influenced by the location of the bony defect and its relationship to surrounding tegmen topography as seen on computed tomography. There are currently no agreed-upon methods of characterizing these radiologic findings. We propose a formal radiologic classification system of SCD based on dehiscence location and adjacent tegmen topography. Study Design: Retrospective case review Setting: Tertiary, neurotology referral center Patients: We identified 298 patients with superior canal dehiscence on CT from February 2001 to October 2013. Of these, 251 had symptomatic superior canal dehiscence syndrome and were included in the study. Intervention: Patients underwent high-resolution temporal bone CT scans with creation of axial, coronal, Poschl, and Stenver reformatted images to examine the superior semicircular canal. Two residents-in-training and a head and neck radiologist independently read the scans. Main Outcome Measures: CT scans were assessed for (1) superior canal dehiscence or "near" dehiscence, (2) defect location relative to the skull base, (3) surrounding tegmen defects, (4) geniculate ganglion dehiscence, (5) superior petrosal sinus-associated dehiscence (SPS), (6) low-lying tegmen, and (7) the distance between the outer table of the temporal bone and the arcuate eminence.
    No preview · Article · Aug 2014 · Otology & Neurotology
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    ABSTRACT: Purpose Vestibular schwannomas (VS) are often followed without initial therapeutic intervention because many tumors do not grow and radiation therapy is associated with potential adverse effects. In an effort to determine whether maximizing initial surveillance predicts for later treatment response, the predictive value of preirradiation growth rate of VS on response to radiation therapy was assessed. Methods and Materials Sixty-four patients with 65 VS were treated with single-fraction stereotactic radiation surgery or fractionated stereotactic radiation therapy. Pre- and postirradiation linear expansion rates were estimated using volumetric measurements on sequential magnetic resonance images (MRIs). In addition, postirradiation tumor volume change was classified as demonstrating shrinkage (ratio of volume on last follow-up MRI to MRI immediately preceding irradiation <80%), stability (ratio 80%-120%), or expansion (ratio >120%). The median pre- and postirradiation follow-up was 20.0 and 27.5 months, respectively. Seven tumors from neurofibromatosis type 2 (NF2) patients were excluded from statistical analyses. Results In the 58 non-NF2 patients, there was a trend of correlation between pre- and postirradiation volume change rates (slope on linear regression, 0.29; P=.06). Tumors demonstrating postirradiation expansion had a median preirradiation growth rate of 89%/year, and those without postirradiation expansion had a median preirradiation growth rate of 41%/year (P=.02). As the preirradiation growth rate increased, the probability of postirradiation expansion also increased. Overall, 24.1% of tumors were stable, 53.4% experienced shrinkage, and 22.5% experienced expansion. Predictors of no postirradiation tumor expansion included no prior surgery (P=.01) and slower tumor growth rate (P=.02). The control of tumors in NF2 patients was only 43%. Conclusions Radiation therapy is an effective treatment for VS, but tumors that grow quickly preirradiation may be more likely to increase in size. Clinicians should take into account tumor growth rate when counseling patients about treatment options.
    No preview · Article · May 2014 · International journal of radiation oncology, biology, physics
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    ABSTRACT: Here we report on advances toward a miniaturized, fully-integrated intracochlear drug-delivery micropump and controller. Our device is designed to be worn as a head mount for Guinea-pig animal models (with the ultimate goal of generating an implantable device for humans) that delivers liquid-solubilized drug through a cannula to the inner ear. Our completed platform will have infuse-withdraw capabilities, and an integrated drug reservoir. Here we present experimental data demonstrating the performance of a simplified version of the device, which has no drug reservoir and is operated only in infusion mode (though it is capable of withdrawing fluid as well). We show that our device successfully delivers the desired infusion profile in a Guinea pig model.
    No preview · Conference Paper · Apr 2014
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    ABSTRACT: Importance: The etiology of superior canal dehiscence (SCD) involving the arcuate eminence is not completely understood, but genetic factors may play a role. One hypothesis is that patients are born with a defect of the superior canal, and an acute event (such as head trauma) or progressive loss of bone (eg, due to dural pulsations) may result in the onset of SCD symptoms. Familial SCD has only been briefly mentioned in the literature to date. Observations: We report 3 families that each had 2 members with SCD syndrome. We found that first-degree relatives presented with similar complaints and that temporal bone computed tomography scans between relatives showed very similar skull base topography and anatomic SCD defects. Conclusions and relevance: The presence of symptomatic SCD among first-degree relatives and similar skull base topography suggests that genetics may play a role in the etiology of SCD.
    Full-text · Article · Feb 2014 · JAMA Otolaryngology - Head and Neck Surgery
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    ABSTRACT: Given the presence of a pathological immune response in sporadic vestibular schwannoma (sVS), this study aims to explore the roles of aspirin in minimizing sVS growth in vivo. Retrospective case review. Tertiary care hospital. People diagnosed with sVS and followed at a tertiary referral center by serial magnetic resonance imaging (MRI) for at least 4 months within the period of January 1980 through April 2012. Patient use of aspirin and sVS growth rate measured by changes in the largest tumor dimension as noted on serial MRIs Within a set of 689 cases, 347 were followed by serial MRI scans (50.3%); of the latter, 81 took aspirin, of which, 33 demonstrated sVS growth, and 48 did not. Of the 266 nonaspirin users, 154 demonstrated sVS growth, and 112 did not. A significant inverse association was found among aspirin users and sVS growth (odds ratio [OR]: 0.50, 95% confidence interval [CI]: 0.29-0.85), which was not confounded by age or sex. Our results suggest a potential therapeutic role of aspirin in inhibiting sVS growth.
    Full-text · Article · Feb 2014 · Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology

  • No preview · Article · Oct 2013 · Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
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    ABSTRACT: Background: Ménière’s disease (MD) is a debilitating disorder of the inner ear characterized by cochlear and vestibular dysfunction. The cause of this disease is still unknown, and epidemiological data for MD are sparse. From the existing literature, women seem to be more susceptible than men, and Caucasians seem to be more susceptible than Asians. Objective: In this article, we characterize a large definite MD cohort for sex and age of onset of disease and use molecular genetic methodologies to characterize ethnicity. Study Design: Medical record review for sex and age of onset. Ancestry analysis compared results from the principal component analysis of whole-genome genotype data from MD patients to self-identified ancestry in control samples. Setting: House Clinic in Los Angeles. Patients: Definitive MD patients. Results: Our review of medical records for definitive MD patients reveals that women are more susceptible than men. We also find that men and women have nearly identical age of onset for disease. Lastly, interrogation of molecular genetic data with principal component analysis allowed detailed observations about the ethnic ancestry of our patients. Comparison of the ethnicity of MD patients presenting to our tertiary care clinic with the self-recollected ethnicity of all patients visiting the clinic revealed an ethnic bias, with Caucasians presenting at a higher frequency than expected and the remaining major ethnicities populating Los Angeles (Hispanics, Blacks, and Asians) presenting at a lower frequency than expected. Conclusion: To the best of our knowledge, this report is the first ethnic characterization of a large MD cohort from a large metropolitan region using molecular genetic data. Our data suggest that there is a bias in sex and ethnic susceptibility to this disease.
    No preview · Article · Sep 2013 · Otology & Neurotology
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    ABSTRACT: HYPOTHESIS: We hypothesize that the severity of hearing loss (HL) associated with sporadic vestibular schwannomas (VS) is correlated with tumor secretion of proteins with ototoxic or otoprotective potential. BACKGROUND: Because the recognition that HL associated with VS is not solely due to compression of the auditory nerve, elucidating the mechanism by which VS cause HL has been an important task. We previously showed that VS stratified by hearing have differential gene expression. We now focus on identifying differentially expressed proteins in tumor secretions. METHODS: Fresh surgical specimens of VS were incubated in sterile PBS at 37°C to collect secretions. The specimens were divided into a group associated with good hearing (GH, word recognition ≥70% and pure-tone average ≤30 dB, n = 11) or poor hearing (PH, n = 10). The groups were compared using a customized cytokine array. Statistically significant results were verified with an enzyme-linked immunosorbent assay on a different set of secretions (n = 8 for GH and n = 10 for PH group). RESULTS: Of the 37 molecules we studied, 9 were significantly expressed in secretions from VS compared with secretions from control nerves. Secretion of fibroblast growth factor 2 (FGF2) was 3.5-fold higher in VS associated with GH versus PH based on cytokine array analysis (p = 0.02), which was validated with enzyme-linked immunosorbent assay. CONCLUSION: This study highlights FGF2, a mitogen known to protect the auditory nerve, as a potential tumor-secreted mediator of hearing protection in VS. If FGF2's significant role in hearing protection in patients with VS is validated, then FGF2 could be used as a biomarker for HL in VS, and therapeutic targeting of the FGF2 signaling pathway may reduce HL due to VS.
    Full-text · Article · Mar 2013 · Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
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    ABSTRACT: OBJECTIVES/HYPOTHESIS: To determine the utility of cervical vestibular evoked myogenic potential (cVEMP) thresholds in the surgical management of bilateral superior canal dehiscence syndrome (SCDS). STUDY DESIGN: Retrospective review. METHODS: We identified patients who underwent surgical treatment for SCDS from our database of 147 patients diagnosed with superior canal dehiscence (SCD) between 2000 and 2011 at our institution. The diagnosis of SCDS was based on clinical signs and symptoms, audiometric and cVEMP testing, and high-resolution computed tomography. RESULTS: We identified 38 patients who underwent SCD surgery in 40 ears (2 bilateral). In seven patients with bilateral SCD, the more symptomatic ear had lower cVEMP thresholds, a larger air bone gap and a lateralizing tuning fork. In 13 patients with perioperative cVEMP testing, thresholds increased in 12 patients following primary repair, and no threshold shift was seen in one patient with persistence of symptoms after revision surgery. Audiometric data showed a significant mean decrease of the low-frequency air-bone gap and a mild (high-frequency) bone conduction loss after surgical repair. CONCLUSIONS: We found that, 1) preoperative cVEMP thresholds, the magnitude of the air-bone gap and tuning-fork testing are important to confirm the worse ear in patients with bilateral SCD, 2) elevation of cVEMP thresholds following surgery correlates with improvement of symptoms and underscores the importance of postoperative testing in patients with bilateral disease or recurrence of symptoms and, 3) SCD plugging is associated with a partial closure of the air-bone gap and a mild (high-frequency) sensorineural hearing loss.
    Full-text · Article · Jan 2013 · The Laryngoscope
  • Michael J. McKenna

    No preview · Article · Jan 2013 · Otology & Neurotology
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    ABSTRACT: Until now, the use of computed tomography (CT) in the diagnosis and evaluation of otosclerosis has been based on correlation of radiologic findings to patient histories, intraoperative examinations, and audiologic data. The purpose of this study was to compare CT findings in otosclerosis to histopathology. Prospective blinded. Radiology department in a tertiary referral hospital and otopathology laboratory. Temporal bones from patients with otosclerosis and other otologic diseases (used as controls). Blinded review of specimen CT scans by radiologists and comparison of CT findings to histopathology of the same bones. Ability of CT to diagnose otosclerosis, identify otosclerotic foci in defined zones of the otic capsule, determine endosteal layer involvement, oval window (OW) obliteration, and round window (RW) obliteration. In a randomized blinded evaluation, radiologists identified 8 of 10 bones with otosclerosis and made 3 false-positive diagnoses from the 36 control bones. Radiologic examination correctly identified otosclerosis anterior to the oval window, in the pericochlear area, and in the round window niche in 17 of 17, 9 of 11, and 3 of 6 bones, respectively. CT correctly determined involvement of the endosteal layer, OW obliteration, and RW obliteration in 5 of 8, 2 of 2, and 2 of 2 temporal bones. High-resolution CT is highly sensitive and specific for the diagnosis of otosclerosis when compared with histopathology. Very small and subtle otosclerotic foci seen on pathology may be missed on CT. Although CT was able to positively identify cochlear endosteal margin involvement, the false-negative rate on CT was significant.
    No preview · Article · Jan 2013 · Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
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    ABSTRACT: To evaluate hearing outcomes in patients treated with third generation bisphosphonates for otosclerosis-related sensorineural hearing loss (SNHL). Otosclerosis is a disease of abnormal bone remodeling in the otic capsule. In recent years, third generation bisphosphonates, with more powerful anti-resorptive properties and increased bone affinity, have demonstrated effectiveness in the treatment of osteoporosis and other metabolic bone diseases. We hypothesized that newer generation bisphosphonates, such as risedronate and zoledronate, would be effective in slowing the progression of SNHL in patients with otosclerosis. Retrospective review. Tertiary referral center, ambulatory care. Risedronate or zoledronate administration. Bone conduction pure tone threshold averages (PTAs) and word recognition (WR) scores were examined for each ear before and after bisphosphonate treatment. Criteria for significant change were defined as greater than 10 decibels in PTA or between 4% and 18% in WR based on binomial variance. All 10 patients had audiometric progression of SNHL in the pretreatment monitoring interval and 12 ears met criteria for significant progression. All 10 patients (19 ears) showed at least no significant progression of SNHL (i.e., stabilization) at an average follow-up of 13 months. Two patients (3 ears) showed improvement by defined audiometric criteria. There were no major complications. Treatment with zoledronate or risedronate stabilized progressive SNHL related to otosclerosis in this small group of patients. Further evaluation of third-generation bisphosphonate treatments is warranted.
    No preview · Article · Aug 2012 · Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology

Publication Stats

3k Citations
240.32 Total Impact Points


  • 2004-2015
    • Harvard University
      Cambridge, Massachusetts, United States
    • University of Wales
      Cardiff, Wales, United Kingdom
  • 1995-2014
    • Harvard Medical School
      • • Department of Otology and Laryngology
      • • Department of Genetics
      • • Department of Radiology
      Boston, Massachusetts, United States
  • 1992-2014
    • Massachusetts Eye and Ear Infirmary
      • • Department of Otolaryngology
      • • Laryngology Division
      Boston, Massachusetts, United States
  • 2007
    • University of Texas Medical Branch at Galveston
      Galveston, Texas, United States
  • 1997-2002
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
    • University of Massachusetts Medical School
      Worcester, Massachusetts, United States
  • 1996-1997
    • Massachusetts General Hospital
      • Department of Oral and Maxillofacial Surgery
      Boston, Massachusetts, United States